Abstract
Asthma is thought to result from an abnormal expansion of CD4 T cells reactive with airborne allergens, and pathology is controlled by several cytokines of the T helper type 2 (Th2) family. The exact molecules which are involved in generating allergen-reactive T cells are not clear. Studies with blocking reagents or knockout animals have shown that the CD28/B7 interaction partially controls development of allergic asthma in mouse models, but may not be the sole molecule involved. In this report, we have investigated the role of the tumor necrosis factor receptor family member OX40 in allergic inflammation using OX40-deficient mice. OX40 has been shown to participate in regulating clonal expansion and memory development of CD4 T cells and may synergize with CD28. Our studies demonstrate that OX40-/- mice, primed with the model allergen ovalbumin and challenged through the airways with aerosolized antigen, are severely impaired in their ability to generate a Th2 response characterized by high levels of interleukin (IL)-5, IL-4, and immunoglobulin E. Moreover, OX40-/- mice exhibit diminished lung inflammation, including an 80-90% reduction in eosinophilia and mucus production, less goblet cell hyperplasia, and significantly attenuated airway hyperreactivity. These studies highlight the potential importance of OX40 in development of allergic asthma and suggest that targeting OX40 may prove useful therapeutically.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 387-392 |
| Number of pages | 6 |
| Journal | Journal of Experimental Medicine |
| Volume | 193 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 5 2001 |
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Keywords
- Allergy
- Asthma
- Costimulation
- Inflammation
- OX40
ASJC Scopus subject areas
- Immunology
Cite this
Development of allergic inflammation in a murine model of asthma is dependent on the costimulatory receptor OX40. / Jember, Amha Gebre Hiwot; Zuberi, Riaz; Liu, Fu-Tong; Croft, Michael.
In: Journal of Experimental Medicine, Vol. 193, No. 3, 05.02.2001, p. 387-392.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Development of allergic inflammation in a murine model of asthma is dependent on the costimulatory receptor OX40
AU - Jember, Amha Gebre Hiwot
AU - Zuberi, Riaz
AU - Liu, Fu-Tong
AU - Croft, Michael
PY - 2001/2/5
Y1 - 2001/2/5
N2 - Asthma is thought to result from an abnormal expansion of CD4 T cells reactive with airborne allergens, and pathology is controlled by several cytokines of the T helper type 2 (Th2) family. The exact molecules which are involved in generating allergen-reactive T cells are not clear. Studies with blocking reagents or knockout animals have shown that the CD28/B7 interaction partially controls development of allergic asthma in mouse models, but may not be the sole molecule involved. In this report, we have investigated the role of the tumor necrosis factor receptor family member OX40 in allergic inflammation using OX40-deficient mice. OX40 has been shown to participate in regulating clonal expansion and memory development of CD4 T cells and may synergize with CD28. Our studies demonstrate that OX40-/- mice, primed with the model allergen ovalbumin and challenged through the airways with aerosolized antigen, are severely impaired in their ability to generate a Th2 response characterized by high levels of interleukin (IL)-5, IL-4, and immunoglobulin E. Moreover, OX40-/- mice exhibit diminished lung inflammation, including an 80-90% reduction in eosinophilia and mucus production, less goblet cell hyperplasia, and significantly attenuated airway hyperreactivity. These studies highlight the potential importance of OX40 in development of allergic asthma and suggest that targeting OX40 may prove useful therapeutically.
AB - Asthma is thought to result from an abnormal expansion of CD4 T cells reactive with airborne allergens, and pathology is controlled by several cytokines of the T helper type 2 (Th2) family. The exact molecules which are involved in generating allergen-reactive T cells are not clear. Studies with blocking reagents or knockout animals have shown that the CD28/B7 interaction partially controls development of allergic asthma in mouse models, but may not be the sole molecule involved. In this report, we have investigated the role of the tumor necrosis factor receptor family member OX40 in allergic inflammation using OX40-deficient mice. OX40 has been shown to participate in regulating clonal expansion and memory development of CD4 T cells and may synergize with CD28. Our studies demonstrate that OX40-/- mice, primed with the model allergen ovalbumin and challenged through the airways with aerosolized antigen, are severely impaired in their ability to generate a Th2 response characterized by high levels of interleukin (IL)-5, IL-4, and immunoglobulin E. Moreover, OX40-/- mice exhibit diminished lung inflammation, including an 80-90% reduction in eosinophilia and mucus production, less goblet cell hyperplasia, and significantly attenuated airway hyperreactivity. These studies highlight the potential importance of OX40 in development of allergic asthma and suggest that targeting OX40 may prove useful therapeutically.
KW - Allergy
KW - Asthma
KW - Costimulation
KW - Inflammation
KW - OX40
UR - http://www.scopus.com/inward/record.url?scp=0035808782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035808782&partnerID=8YFLogxK
U2 - 10.1084/jem.193.3.387
DO - 10.1084/jem.193.3.387
M3 - Article
C2 - 11157058
AN - SCOPUS:0035808782
VL - 193
SP - 387
EP - 392
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 3
ER -